To study the factors that regulate synaptic connections in the developing neocortex, the Stryker laboratory will study transgenic mice with targeted disruptions of genes whose products are involved in synaptic plasticity. The major research goals are (1) to delineate the role of TrkB neurotrophin signaling in activity-dependent plasticity in the visual cortex, using mice defective in TrkB in specific populations of neurons and mice in which the expression of BDNF is temporally regulated; (2) to determine the role of the autophosphorylation and possible dendritic synthesis of calcium calmodulin kinase type II in the induction and maintenance of activity-dependent plasticity in the visual cortex using transgenic mice defective in these processes, and (3) to survey the roles of a number of molecules important for neuronal pathfinding and specification of cortical topography using a novel mapping technique to measure the size and topographic organization of primary visual cortex and 4 higher cortical visual areas in inducible transgenic knockout mice. We expect that if the roles of these molecules turn out to be important and more than merely permissive in activity-dependent plasticity, the new understanding of cortical plasticity would have important implications for our understanding of common neurodevelopmental abnormalities and hence for candidate therapies.